微小RNA在增生性瘢痕中的作用及其机制研究进展

田文融; 左俊; 艾江; 齐郁松; 卜盼盼; 赵皎均; 余扬; 马少林

doi:10.3760/cma.j.cn501225-20220508-00179

微小RNA在增生性瘢痕中的作用及其机制研究进展

doi: 10.3760/cma.j.cn501225-20220508-00179

新疆医科大学第一附属医院整形外科，乌鲁木齐　　830011

基金项目:

国家自然科学基金地区科学基金项目 81760345

自治区研究生科研创新项目 XJ2919G202, XJ2022G174

详细信息

通讯作者:
马少林，Email：mashaolin9@163.com

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- 被引次数: 0
出版历程
- 收稿日期: 2022-05-08

Research advances on the role and mechanism of microRNA in hypertrophic scar

Department of Plastic Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China

Funds:

Regional Science Foundation Project of National Natural Science Foundation of China 81760345

Autonomous Region Postgraduate Scientific Research Innovation Project XJ2919G202, XJ2022G174

More Information

Corresponding author: Ma Shaolin, Email: mashaolin9@163.com

摘要

摘要: 增生性瘢痕（HS）影响患者功能与美观，给患者带来沉重的心理负担，但其具体的分子生物学水平发病机制尚不明确，因此该病仍然是临床难防难治疾病之一。微小RNA（miR）是一类具有调节基因表达作用的单链内源性非编码RNA。miR在HS的成纤维细胞内的异常转录可影响下游信号通路或蛋白的转导与表达，对miR及其下游信号通路、蛋白的探究有助于深入了解瘢痕增生的发生和发展机制。该文总结并分析近年来miR与多种信号通路如何参与HS的形成与发展，并进一步概述miR与HS中靶基因之间的相互作用。
- 瘢痕 /
- 微RNAs /
- MAP激酶信号系统 /
- 肿瘤坏死因子-β-Smad信号通路 /
- 磷脂酰肌醇-3-激酶-蛋白激酶B-哺乳动物雷帕霉素靶蛋白信号通路
Abstract: Hypertrophic scar (HS) affects the function and beauty of patients, and brings a heavy psychological burden to patients. However, the specific pathogenesis mechanism of HS in molecular biology level is not yet clear, and this disease is still one of the clinical diseases difficult to prevent and cure. MicroRNA (miR) is a family of single-stranded endogenous noncoding RNAs that can regulate gene expression. The abnormal transcription of miR in hypertrophic scar fibroblasts can affect the transduction and expression of downstream signal pathway or protein, and the exploration of miR and its downstream signal pathway and protein helps deeply understand the occurrence and development mechanism of scar hyperplasia. This article summarized and analyzed how miR and multiple signal pathways involve in the formation and development of HS in recent years, and further outlined the interaction between miR and target genes in HS.
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参考文献(47)

[1]	LimandjajaGC,NiessenFB,ScheperRJ,et al.Hypertrophic scars and keloids: overview of the evidence and practical guide for differentiating between these abnormal scars[J].Exp Dermatol,2021,30(1):146-161.DOI: 10.1111/exd.14121.
[2]	FinnertyCC,JeschkeMG,BranskiLK,et al.Hypertrophic scarring: the greatest unmet challenge after burn injury[J].Lancet,2016,388(10052):1427-1436.DOI: 10.1016/S0140-6736(16)31406-4.
[3]	LvK,XiaZ,Chinese consensus panel on the prevention and treatment of scars.Chinese expert consensus on clinical prevention and treatment of scar[J/OL].Burns Trauma,2018,6:27[2020-05-08].https://pubmed.ncbi.nlm.nih.gov/30263894/.DOI: 10.1186/s41038-018-0129-9.
[4]	PotekaevNN,BorzykhOB,MedvedevGV,et al.The role of extracellular matrix in skin wound healing[J].J Clin Med,2021,10(24):5947.DOI: 10.3390/jcm10245947.
[5]	LeeHJ,JangYJ.Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids[J].Int J Mol Sci,2018,19(3):711.DOI: 10.3390/ijms19030711.
[6]	MengXM,Nikolic-PatersonDJ,LanHY.TGF-β: the master regulator of fibrosis[J].Nat Rev Nephrol,2016,12(6):325-338.DOI: 10.1038/nrneph.2016.48.
[7]	HerterEK,XuLandén N.Non-coding RNAs: new players in skin wound healing[J].Adv Wound Care (New Rochelle),2017,6(3):93-107.DOI: 10.1089/wound.2016.0711.
[8]	La RoccaG,KingB,ShuiB,et al.Inducible and reversible inhibition of miRNA-mediated gene repression in vivo[J].Elife,2021,10:e70948.DOI: 10.7554/eLife.70948.
[9]	WangX,HeY,MackowiakB,et al.MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases[J].Gut,2021,70(4):784-795.DOI: 10.1136/gutjnl-2020-322526.
[10]	WonnacottA,DenbyL,CowardRJM,et al.MicroRNAs and their delivery in diabetic fibrosis[J].Adv Drug Deliv Rev,2022,182:114045.DOI: 10.1016/j.addr.2021.114045.
[11]	Gallant-BehmCL,PiperJ,LynchJM,et al.A microRNA-29 mimic (remlarsen) represses extracellular matrix expression and fibroplasia in the skin[J].J Invest Dermatol,2019,139(5):1073-1081.DOI: 10.1016/j.jid.2018.11.007.
[12]	ChenQ,ZhaoT,XieX,et al.MicroRNA-663 regulates the proliferation of fibroblasts in hypertrophic scars via transforming growth factor-β1[J].Exp Ther Med,2018,16(2):1311-1317.DOI: 10.3892/etm.2018.6350.
[13]	张权,白泽明,陶凯.miR-133a抑制增生性瘢痕成纤维细胞增殖及相关蛋白表达[J].中国美容整形外科杂志,2021,32(11):658-661,681.DOI: 10.3969/j.issn.1673-7040.2021.11.006.
[14]	QiJ,LiuY,HuK,et al.MicroRNA-26a inhibits hyperplastic scar formation by targeting Smad2[J].Exp Ther Med,2018,15(5):4332-4338.DOI: 10.3892/etm.2018.5984.
[15]	QiJ,LiuY,HuK,et al.MicroRNA-205-5p regulates extracellular matrix production in hyperplastic scars by targeting Smad2[J].Exp Ther Med,2019,17(3):2284-2290.DOI: 10.3892/etm.2019.7187.
[16]	XiaoY.MiR-486-5p inhibits the hyperproliferation and production of collagen in hypertrophic scar fibroblasts via IGF1/PI3K/AKT pathway[J].J Dermatolog Treat,2021,32(8):973-982.DOI: 10.1080/09546634.2020.1728210.
[17]	ShenW,WangY,WangD,et al.miR-145-5p attenuates hypertrophic scar via reducing Smad2/Smad3 expression[J].Biochem Biophys Res Commun,2020,521(4):1042-1048.DOI: 10.1016/j.bbrc.2019.11.040.
[18]	ZhouX,XieY,XiaoH,et al.MicroRNA-519d inhibits proliferation and induces apoptosis of human hypertrophic scar fibroblasts through targeting Sirtuin 7[J].Biomed Pharmacother,2018,100:184-190.DOI: 10.1016/j.biopha.2018.01.158.
[19]	LiZ,WangP,ZhangJ,et al.MicroRNA-497-5p downregulation inhibits cell viability, reduces extracellular matrix deposition and induces apoptosis in human hyperplastic scar fibroblasts by regulating Smad7[J].Exp Ther Med,2021,21(4):384.DOI: 10.3892/etm.2021.9815.
[20]	郭冰玉,林枫,白泽明,等.微小RNA-296在兔增生性瘢痕中的表达及对人成纤维细胞的作用[J].中华烧伤杂志,2021,37(8):725-730.DOI: 10.3760/cma.j.cn501120-20210420-00142.
[21]	ZhangZ,GaoX,HeY,et al.MicroRNA-411-3p inhibits bleomycin-induced skin fibrosis by regulating transforming growth factor-β/Smad ubiquitin regulatory factor-2 signalling[J].J Cell Mol Med,2021,25(24):11290-11299.DOI: 10.1111/jcmm.17055.
[22]	YuanR,DaiX,LiY,et al.Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-β2/Smad3 signaling[J].Mol Med Rep,2021,24(5):758.DOI: 10.3892/mmr.2021.12398.
[23]	LiY,ZhangJ,ZhangW,et al.MicroRNA-192 regulates hypertrophic scar fibrosis by targeting SIP1[J].J Mol Histol,2017,48(5/6):357-366.DOI: 10.1007/s10735-017-9734-3.
[24]	LiY,ZhangJ,ShiJ,et al.Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis[J].Stem Cell Res Ther,2021,12(1):221.DOI: 10.1186/s13287-021-02290-0.
[25]	MuS,KangB,ZengW,et al.MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway[J].Mol Cell Biochem,2016,416(1/2):99-108.DOI: 10.1007/s11010-016-2699-9.
[26]	WuX,LiJ,YangX,et al.miR-155 inhibits the formation of hypertrophic scar fibroblasts by targeting HIF-1α via PI3K/AKT pathway[J].J Mol Histol,2018,49(4):377-387.DOI: 10.1007/s10735-018-9778-z.
[27]	郭冰玉,姜栋文,回蔷,等.微小RNA-205在人增生性瘢痕中的表达及作用[J].中华烧伤杂志,2021,37(2):180-186.DOI: 10.3760/cma.j.cn501120-20200219-00071.
[28]	ZhangJ,ZhouQ,WangH,et al.MicroRNA-130a has pro-fibroproliferative potential in hypertrophic scar by targeting CYLD[J].Arch Biochem Biophys,2019,671:152-161.DOI: 10.1016/j.abb.2019.07.003.
[29]	ZhouY,ShiX,LiS,et al.microRNA-181a promotes the proliferation of hypertrophic scar fibroblasts and inhibits their apoptosis via targeting phosphatase and tensin homolog[J].Ann Palliat Med,2021,10(4):4563-4571.DOI: 10.21037/apm-21-604.
[30]	HeT,ZhangY,LiuY,et al.MicroRNA-494 targets PTEN and suppresses PI3K/AKT pathway to alleviate hypertrophic scar formation[J].J Mol Histol,2019,50(4):315-323.DOI: 10.1007/s10735-019-09828-w.
[31]	罗滨林,张轩龙,姚刚.MicroRNA在增生性瘢痕中的研究进展[J].医学综述,2020,26(21):4200-4206.DOI: 10.3969/j.issn.1006-2084.2020.21.009.
[32]	DongS,SunY.MicroRNA-22 may promote apoptosis and inhibit the proliferation of hypertrophic scar fibroblasts by regulating the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/p21 pathway[J].Exp Ther Med,2017,14(4):3841-3845.DOI: 10.3892/etm.2017.4942.
[33]	LiuB,GuoZ,GaoW.miR-181b-5p promotes proliferation and inhibits apoptosis of hypertrophic scar fibroblasts through regulating the MEK/ERK/p21 pathway[J].Exp Ther Med,2019,17(3):1537-1544.DOI: 10.3892/etm.2019.7159.
[34]	WeiS,QiuY.MiR-210-5p regulates STAT3 activation by targeting STAT5A in the differentiation of dermal fibroblasts[J].3 Biotech,2021,11(5):243.DOI: 10.1007/s13205-021-02777-w.
[35]	贺茜,马芳,万瑀,等.miR-382-3p抑制人增生性瘢痕成纤维细胞的增殖[J].中国组织工程研究,2023,27(11):1758-1764.
[36]	GuS,HuangX,XuX,et al.Inhibition of CUB and sushi multiple domains 1 (CSMD1) expression by miRNA-190a-3p enhances hypertrophic scar-derived fibroblast migration in vitro[J].BMC Genomics,2021,22(1):613.DOI: 10.1186/s12864-021-07920-8.
[37]	ZhangZ,HuangX,YangJ,et al.Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars[J].J Transl Med,2021,19(1):451.DOI: 10.1186/s12967-021-03091-y.
[38]	LiC,ZhuHY,BaiWD,et al.MiR-10a and miR-181c regulate collagen type I generation in hypertrophic scars by targeting PAI-1 and uPA[J].FEBS Lett,2015,589(3):380-389.DOI: 10.1016/j.febslet.2014.12.024.
[39]	ZhangQ,GuoB,HuiQ,et al.miR-137 inhibits proliferation and metastasis of hypertrophic scar fibroblasts via targeting pleiotrophin[J].Cell Physiol Biochem,2018,49(3):985-995.DOI: 10.1159/000493236.
[40]	郭冰玉,林枫,回蔷,等.微小RNA-627在人增生性瘢痕中的表达及作用[J].中华烧伤杂志,2021,37(4):369-376.DOI: 10.3760/cma.j.cn501120-20200225-00090.
[41]	ChaiCY,TaiIC,ZhouR,et al.MicroRNA-9-5p inhibits proliferation and induces apoptosis of human hypertrophic scar fibroblasts through targeting peroxisome proliferator-activated receptor β[J].Biol Open,2020,9(12):bio051904.DOI: 10.1242/bio.051904.
[42]	LiL,HanW,ChenY,et al.MiR-3613-3p inhibits hypertrophic scar formation by down-regulating arginine and glutamate-rich 1[J].Mol Cell Biochem,2021,476(2):1025-1036.DOI: 10.1007/s11010-020-03968-4.
[43]	LiJ,LiY,WangY,et al.Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts[J/OL].Burns Trauma,2021,9:tkab038[2022-05-08].https://pubmed.ncbi.nlm.nih.gov/34859108/.DOI: 10.1093/burnst/tkab038.
[44]	GuoB,HuiQ,XuZ,et al.miR-495 inhibits the growth of fibroblasts in hypertrophic scars[J].Aging (Albany NY),2019,11(9):2898-2910.DOI: 10.18632/aging.101965.
[45]	WangX,ZhangY,JiangBH,et al.Study on the role of Hsa-miR-31-5p in hypertrophic scar formation and the mechanism[J].Exp Cell Res,2017,361(2):201-209.DOI: 10.1016/j.yexcr.2017.09.009.
[46]	ZhangY,HongWL,LiZM,et al.The mechanism of miR-222 targets matrix metalloproteinase 1 in regulating fibroblast proliferation in hypertrophic scars[J].Aesthetic Plast Surg,2021,45(2):749-757.DOI: 10.1007/s00266-020-01727-w.
[47]	LiuF,ChenWW,LiY,et al.MiR-6836-3p promotes proliferation of hypertrophic scar fibroblasts by targeting CTGF[J].Eur Rev Med Pharmacol Sci,2018,22(13):4069-4074.DOI: 10.26355/eurrev_201807_15396.